Major histocompatibility complex (MHC) is a cell surface molecule encoded by a large gene family in all vertebrates. The MHC gene family is divided into three classes: class I; class II; and class III.
MHC class I molecules are found on every nucleated cell of the body. Their function is to present fragments of cytosolic proteins from within the cell to cytotoxic T cells. Cells presenting “self” peptides will be ignored, whereas cells presenting non-self peptides will be recognized and killed by the cytotoxic T cells.
MHC class II molecules are found only on antigen presenting cells (APCs), including macrophages, dendritic cells, and B cells. MHC class II molecules present fragments of extracellular proteins to helper T cells. Cells presenting “self” peptides will be ignored, whereas cells presenting non-self peptides will be recognized by the helper T cells, which help to trigger an appropriate immune response, mainly via production of various cytokines, that may include localized inflammation and swelling due to recruitment of phagocytes or an antibody-mediated immune response due to activation of B cells.
It is known from, for example, International Patent Application Publication No. WO 1995/13092, International Patent Application Publication No. WO 2001/77301 and Berger et al. (J. Pharm. Pharmaceut. Sci., 10(2):144-152, 2007) that interferon (IFN) can be used to increase expression of MHC class I on tumour cells, so that the cells may be used in a cancer vaccine. However, MHCII expression by tumour cells following treatment with IFN is highly variable, with some cells being responsive to IFN treatment and some being unresponsive to IFN treatment. Moreover, any tumour cells that express MHCII could only present self or cancer antigens in the context of MHCI and MHCII. Cancer antigens are not consistently immunogenic, as many are recognized as self antigens. This is particularly true as the cancer develops and becomes more aggressive. The lack of a highly immunogenic antigen being presented in the context of MHCII means that T helper cells will not be activated and a strong and robust immune response cannot be consistently produced by the cancer vaccines of the prior art.
Accordingly, there is a need for alternative therapies to overcome or mitigate at least some of the deficiencies of the prior art.